In contrast, non-thymidine regimens were associated with similar mtDNA levels to ART-naïve controls (median 1675, range: 916–4180 copies/cell, P=0.8), and initiating these regimens was not associated with significant changes in mtDNA over time (mean reduction of 69 copies/cell/month, P=0.6). Among NRTI-experienced patients, switching from stavudine to zidovudine or abacavir was associated with a marked increase in adipocyte mtDNA (3–11-fold increase, P=0.01) over 1–24 months (median 6 months). After adjustment for effects of choice of NRTI therapy in a mixed effects analysis, no significant effects of HIV protease inhibitor therapy (current PI: 38%, P=0.7) nor age (P=0.9) were detected.

CONCLUSION: These data are concordant with evidence that lipoatrophy risk is differentially and specifically associated with stavudine or zidovudine use, providing further evidence that NRTI-induced mitochondrial toxicity is central to lipoatrophy pathogenesis. Alternative NRTI regimens were not associated with adipocyte mtDNA depletion in this study, nor were demographic/disease-related factors.